Best Practices for Prescribing Combination Therapy for Glycemic Control

Las Vegas—Metformin is the recommended initial treatment for patients with type 2 diabetes who are unable to reach glycemic control via lifestyle modifications. Pulling from recent guidelines, John E. Anderson, MD, and Ben Taylor, PhD, PA-C, identified best practices for prescribing second- and third-line diabetes agents and methods to increase compliance when metformin monotherapy fails during a workshop at the CRS meeting.

A number of factors are likely to contribute to the complexities of controlling blood glucose levels in individuals with type 2 diabetes, including the limitations of reactive stepwise treatment, therapy that is not matched to the individual, and conservative prescribing of antidiabetic agents. Drs. Anderson and Taylor noted that no single class of agents targets all key type 2 diabetes pathophysiologies.

The American Diabetes Association (ADA) Standards of Medical Care in Diabetes–2014 recommends a patient-centered approach to guide the choice of pharmacological agents [Diabetes Care. 2014;37(suppl 1):S14-S80]. Considerations include efficacy, cost, potential side effects, effect on weight, comorbidities, hypoglycemia risk, and patient preferences. If patients are not at a targeted glycated hemoglobin (HbA1c) level of <7% after 3 months of noninsulin monotherapy, the ADA recommends the addition of a second oral agent. Due to the progressive nature of type 2 diabetes, many patients will require insulin therapy alone or in combination with other agents to maintain glucose control. Drs. Anderson and Taylor referenced the 2012 ADA/European Association for the Study of Diabetes position statement on the management of hyperglycemia in type 2 diabetes patients, which includes an algorithm of potential sequences of antihyperglycemic therapy [Diabetes Care. 2012;35(6):1364-1379].

The speakers highlighted key points in the rationale for combination therapy:

• Improving metabolic effect by combining drugs with different mechanisms of action
• Reducing side effects by submaximal dosage
• Starting combination therapy according to metabolic guidelines achieves optimal results
• Prescribing drugs according to individual patient need (financial vs therapeutic)

Given the drawbacks of the traditional stepwise approach, there is a strong rationale for earlier use of combination therapy, according to the speakers, who mentioned that earlier introduction of combination therapy offers the potential for therapeutic goals to be achieved more rapidly than with conventional stepwise management, thus reducing the risks associated with extended periods of poor glycemic control. Also, combination therapy with agents with complementary mechanisms of action is likely to have additional benefits for the long-term management of type 2 diabetes.

In addition to insulin, classes of antihyperglycemic therapies include sulfonylureas, thiazolidinediones, glucagon-like peptide-1 receptor agonists, dipeptidyl peptidase-4 inhibitors, and sodium-glucose cotransporter-2 (SGLT-2) inhibitors. Drs. Anderson and Taylor noted that insulin-independent therapies such as SGLT-2 inhibitors enable glucose-lowering and weight loss without increased propensity for hypoglycemia.

Clinicians also need to factor in patient comorbidities when choosing a treatment option. For example, thiazolidinediones should be avoided in diabetes patients with heart failure; however, metformin can be used unless the condition is unstable or severe. Individuals with type 2 diabetes frequently have liver dysfunction, and Drs. Anderson and Taylor cautioned that most diabetes drugs have not been tested in advanced liver disease. Treatment with pioglitazone may help those with steatosis. They said insulin has no restrictions for use in patients with liver impairment; therefore, it is the best option in patients with advanced disease.

Drs. Anderson and Taylor also described strategies to improve diabetes care. They referenced recommendations outlined in the ADA Standards of Medical Care in Diabetes–2014:

• Care should be aligned with components of the Chronic Care Model (CCM) to ensure productive interactions between a prepared proactive practice team and an informed activated patient. The CCM includes 6 core elements for the provision of optimal care of patients with chronic disease: (1) delivery system design; (2) self-management support; (3) decision support; (4) clinical information systems; (5) community resources and policies; and (6) health systems
• When feasible, care systems should support team-based care, community involvement, patient registries, and embedded decision support tools to meet patient needs
• Treatment decisions should be timely and based on evidence-based guidelines that are tailored to individual patient preferences, prognoses, and comorbidities
• A patient-centered communication style should be used that incorporates patient preferences, assesses literacy and numeracy, and addresses cultural
barriers to care—Eileen Koutnik-Fotopoulos